Total Synthesis of the Sex Pheromone of Clania variegata Snellen and Its Stereoisomers

The paulownia bagworm, Clania variegata Snell, is an economically important pest of agriculture and forests. The sex pheromone of this pest and its stereoisomers were synthesized, and two of the stereoisomers were prepared for the first time. Our strategy was efficient and mainly included the ring-opening reaction of (S)-2-methyloxirane, the coupling of chiral sulfonate, the oxidative cleavage of olefin, and Yamaguchi esterification. Moreover, the overall yields of our synthesis were 23–29%, with eight steps in the longest route.


Introduction
The paulownia bagworm, Clania variegata Snell (synonyms for Eumeta japonica and Eumeta variegata), has become an economically important pest of agriculture and forests [1,2].This pest is distributed in Australia, Korea [3], China, Indonesia [4], and Japan [5].The larvae mainly defoliate various trees including apple, pear, peach, walnut, empress tree, gingko, and mulberry, and they also damage many agricultural crops, such as tea, citrus, coffee, loquat, maize, cotton, and soybean [6,7].Due to it living within a self-enclosing bag coated with silk throughout all life stages [8,9], it is difficult to control the paulownia bagworm.
Sex pheromones have become an important component for the integrated pest management of agricultural pests, which has the advantages of being environmentally benign, highly efficient, and showing a lack of toxicity to mammals [10,11].In 2006, Gries identified (S)-2-methylpentan-3-yl 3,13-dimethylpentadecanoate as a major component of the sex pheromone of Clania variegata Snellen by gas chromatographic electroantennographic detection (GC-EAD) analyses and field trapping experiments [7].Later, Mori prepared four stereoisomers of (S)-2-methylpentan-3-yl 3,13-dimethylpentadecanoate via olefin cross metathesis, and their bioassay revealed the (3R,13R,3 ′ S)-isomer (1a) as the bioactive one [12,13].Other total syntheses of the sex pheromone are based on the S N 2 reactions of secondary sulfonates and Evans template inductions [14,15].To search for a more efficient synthesis method for the sex pheromone of Clania vartegata Snel, and provide stereoisomers for further biological research, herein, a new and concise synthesis of the sex pheromone of Clania variegata Snellen and its stereoisomers using Chiral Pool (Figure 1) has been developed.

Conclusions
In summary, we have achieved a novel and efficient total synthesis method for the sex pheromone of Clania variegata Snellen and its stereoisomers.Furthermore, (R)-2methylpentan-3-yl (3R,13R)-3,13-dimethylpentadecanoate (1c) and (R)-2-methylpentan-3-yl (3R,13S)-3,13-dimethylpentadecanoate (1d) were prepared for the first time.The core synthetic strategy involved the ring-opening reaction of (S)-2-methyloxirane, the coupling of chiral sulfonate, the oxidative cleavage of olefin, and Yamaguchi esterification.Compared with previous approaches, our synthesis method has the advantages of being more concise (eight steps in the longest route) and resulting in a higher overall yield (23-29%).Moreover, this synthetic sex pheromone and its stereoisomers would be valuable for control of the paulownia bagworm.

Figure 1 .
Figure 1.The sex pheromone of Clania vartegata Snell and its stereoisomers.

Figure 1 .
Figure 1.The sex pheromone of Clania vartegata Snell and its stereoisomers.

Figure 1 .
Figure 1.The sex pheromone of Clania vartegata Snell and its stereoisomers.